White matter structural network disturbances in first-episode, drug-naïve adolescents with generalized anxiety...

Previous studies have suggested that individuals with generalized anxiety disorder (GAD) would show inefficient whole-brain communication and dysconnectivity in the fronto-parietal-subcortical sub-networks in the white matter (WM) structural network. However, these hypotheses have yet to be tested.

Individual WM structural networks were constructed based on diffusion MRI data and deterministic tractography in 34 first-episode, medication-naïve adolescents with GAD and 27 healthy controls (HCs). Graph theory was applied to investigate the topological organization alterations of the structural network.

GAD patients showed disrupted small-world configurations (i.e., increased path length and decreased clustering coefficient) and hub organization (i.e., less connection strength in the feeder and local connections). A decreased connection strength was found in a GAD-related sub-network (mainly involving the frontal-subcortical circuits), which was able to distinguish GAD patients from HCs with higher accuracy (area under the curve of 0.96, sensitivity of 94%, specificity of 89%) than clinical scores and other topological alternations.

The current study just compared GAD patients with HCs based on a small sample, leaving whether the alternations found here are specific to GAD still an open question. Future studies are recommended to recruit patients with other anxiety disorders (e.g., social anxiety disorder) and/or comorbid mood disorders to identify the GAD-specific WM alterations using a larger sample.

Our findings highlight the disruption of the topological organization of the whole-brain WM structural network (especially the frontal-subcortical circuits) in GAD, and suggest the potential of using structural connectivity of the GAD-related sub-network as a biomarker for GAD patients.